Mechanism of oxidation of (p-substituted phenylthio)acetic acids with N-bromophthalimide

Article abstract of DOI:10.1155/2011/560357

The kinetics of oxidation of (phenylthio)acetic acid (PTAA) by N-Bromophthalimide (NBP) in acetonitrile-water solvent mixture at 298 K in the presence of perchloric acid has been followed potentiometrically. The reaction is first-order each in NBP and PTA

Full text of DOI:10.1155/2011/560357

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2011, 8(1), 1-8
http://www.e-journals.net
Mechanism of Oxidation of (p-Substituted
Phenylthio)acetic Acids with N-Bromophthalimide
N.M.I. ALHAJI*, A.M. UDUMAN MOHIDEEN and K. KALAIMATHI
P.G and Research Department of Chemistry
Khadir Mohideen College, Adirampattinam-614 701, India
alhajinmi@hotmail.com
Received 25 May 2010; Accepted 31 July 2010
Abstract: The kinetics of oxidation of (phenylthio)acetic acid (PTAA) by
N-Bromophthalimide (NBP) in acetonitrile-water solvent mixture at 298 K in
the presence of perchloric acid has been followed potentiometrically. The
reaction is first-order each in NBP and PTAA and inverse fractional-order in
H+. Also, it has been found that the reaction rate is not affected by changes in
ionic strength of the reaction medium or by the addition of chemicals such as
phthalimide, acrylonitrile and potassium bromide. However, an increase in the
water content of the solvent mixture causes an increase in the rate of reaction.
These observations have been well analyzed in favour of a SN2-type
mechanism, involving NBP itself as the reactive species. Effect of substituents
on the reaction rate has been analysed by employing various (p-sustituted
phenylthio)acetic acids. The electron-releasing substituent in the phenyl ring of
PTAA accelerates the reaction rate while the electron-withdrawing substituent
retards the rate. The excellently linear Hammett plot yields a large negative ρ
value, supporting the involvement a bromosulphonium ion intermediate in the
rate-determining step.
Keywords: Potentiometry, N-Bromophthalimide, (Phenylthio)acetic acid, Oxidation, Bromosulphonium ion.
Introduction
The application of N-halo compounds in the field of organic synthesis is very wide, such as
oxidation reactions, deprotection and protection of different functional groups, halogenation
of saturated and unsaturated compounds, acylation of alcohols, phenols, amines or thiols,
epoxidation of alkenes, aziridination and finding more and more applications1,2. The diverse
nature of the chemistry of these compounds is due to their ability to act as sources of
halonium cations, hypohalite species and nitrogen anions, which act both as bases and
nucleophiles3. A review of literature shows that N-halo compounds such as N-halo-

2
N.M.I. ALHAJI et al.
succinimides4-7, N-halosulphonamides8-11 (chloramine-T, bromamine-T, chloramine-
B, bromamine-B, etc.), N-haloamides12-14 (N-haloacetamides, N-bromobenzamide,
N-chloronicotinamide, etc.), N-halosaccharins15-17 and N-bromophthalimide18,19 are
commonly used for the oxidation of various organic compounds such as alcohols, aldehydes,
amino acids, keto acids, sulphides, etc. However, no detailed kinetic study of oxidation of
(phenylthio)acetic acid with N-bromophthalimide has so far been attempted. Herein we
report the results obtained from a detailed kinetic study on the oxidation of several
(p-substituted phenylthio)acetic acids (p-XC6H4SCH2COOH; X = OCH3, CH3, H, F, Cl or
NO2) with NBP.
Experimental
The (phenylthio)acetic acids were prepared by known methods20 and were purified
by repeated recrystallisations from aqueous ethanol. Doubly distilled water was used
throughout the experiment, the second distillation being from permanganate. AR
grade N-bromophthalimide (Aldrich), perchloric acid (E.Merck) and GR grade
sodium perchlorate were used as received. Acetonitrile was purified21 by refluxing
with P2O5.
Kinetic measurements
The kinetic runs were carried out in 80% acetonitrile - 20% water (v/v) solvent mixture in
acid medium, the acid strength being maintained by the addition of HClO4 and the ionic
strength by NaClO4. The kinetics were followed potentiometrically in a manner as described
earlier22. The emf of the cell was measured periodically using an Equip-Tronics
potentiometer while the reaction mixture was magnetically stirred continuously. The
temperature of the reaction mixture was maintained at the desired value to an accuracy
o
of 0.1 C by circulating thermostated water in the reaction vessel. The pseudo first-order
rate constants (kobs) were calculated from the slopes of ln(Et – E∞) versus time plots (r >
0.990) and the results were reproducible to an accuracy of 5%. The second-order rate
constants (k2) were obtained as kobs/[PTAA].
Product analysis
In a typical experiment, the reaction mixture containing 50 fold excess of PTAA over NBP
was kept overnight under stirring. The solvent was removed by distillation. The residue was
then extracted with ether. The extract was dried over anhydrous sodium sulphate and the
solvent evaporated. The residue was subjected to TLC analysis on a silica gel plate
developed in a solvent system of n-butanol-acetic acid-water (40-10-50%, upper layer was
used). The residue gave two spots, which were made visible by exposure to iodine; one
corresponding to (phenylthio)acetic acid (Rf = 0.84) and the other to phenylsulphinylacetic
acid (Rf = 0.45). Further, the IR spectra of the residue showed an intense absorption band at
1050 cm-1 characteristic of SO stretching frequency. The formation of corresponding
phenylsulphinylacetic acid as the product was also confirmed with other (p-substituted
phenylthio)acetic acids also.
Stoichiometry
In a typical experiment, a reaction mixture containing 10 times excess of NBP over
PTAA was prepared and allowed to react overnight. Then the unreacted NBP was
estimated, which established a 1:1 stoichiometry between NBP and PTAA, as
represented in the Scheme 1.

Mechanism of Oxidation of (p-Substituted Phenylthio)acetic Acids
3
O
PhSCH COOH
PhSCH 2COOH
+
Br
N
O
+
H2O
2
O
H+ + Br −
+
HN
PhSOCH COOH
PhSOCH2COOH
+
O
Scheme 1
Results and Discussion
The kinetics of oxidation of PTAA by NBP was carried out potentiometrically in 80:20
(v/v) acetonitrile-water mixture at 298 K in the presence of perchloric acid at constant
ionic strength under pseudo-first-order conditions ([PTAA] >> [NBP]). The ionic
strength of the medium was maintained by the addition of NaClO4. The pseudo-first-
order rate constants, kobs and the second-order rate constants, k2 at different initial
concentrations of NBP, PTAA and H+ are presented in Table 1. At constant initial
concentration of PTAA, kobs values remain almost constant upon varying the initial
concentration of NBP; this coupled with the observation of linear ln(Et - E∞) versus time
plots ensures that the order of the reaction in NBP is one. Also, the rate data in Table 1
point out that kobs value increases linearly in a first-order fashion with increase in the
initial concentration of PTAA. Similar trend is observed in the kobs and k2 values for the
oxidation of other (p-substituted phenylthio)acetic acids. The constancy of k2 at varying
initial concentrations of PTAA (Table 1) and the excellent linearity of the plot of log
kobs versus log [PTAA] with unit slope (slope = 1.02 0.04, r = 0.997) indicate that the
reaction follows first-order kinetics with respect to [PTAA].
Table 1. Pseudo-first-order and second-order rate constants for the oxidation of PTAA by
NBP in aqueous acetonitrile at 298 Ka,b
103[PTAA]o, M
104[NBP]o, M
104[H+]o, M
1.4
1.4
104 kobsc, s-1
4.19 0.29
8.48 0.68
20.0 1.2
29.9 2.4
43.3 3.9
8.08 0.74
8.24 0.66
8.32 0.70
8.48 0.79
15.8 1.4
13.4 0.8
10.8 1.0
6.62 0.58
102k2 , M-1s-1
41.8 2.9
42.3 3.5
42.5 3.0
42.7 3.4
43.3 3.9
40.6 3.8
41.0 3.3
41.8 3.5
42.3 4.0
79.0 7.0
67.0 4.0
54.0 5.0
33.1 2.9
d
1.0
2.0
4.0
7.0
10.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.0
1.0
1.0
1.0
1.0
0.4
0.7
1.3
1.6
1.0
1.0
1.0
1.0
1.4
1.4
1.4
1.4
1.4
1.4
1.4
0.2
0.6
1.0
2.0
aAs determined by a potentiometric technique following the disappearance of NBP; the error quoted in
k values is the 95% confidence limit of ‘Student t test’23 .bGeneral conditions: [I] = 0.501 M; Solvent =
80:20 (v/v) acetonitrile-water. cEstimated from pseudo-first-order plots over 60% reaction.
dIndividual k2 values estimated as kobs/[PTAA]o
Also, the plot of 1/kobs versus 1/[PTAA] is linear passing through origin (Figure 1), thus
excluding a Michaelis-Menten type of mechanism.

4
N.M.I. ALHAJI et al.
1/ [PTAA]o, M-1
Figure 1. Double reciprocal plot for the oxidation of PTAA with NBP
The kobs values measured at different initial concentrations of H+ for the oxidation of
PTAA (Table 1) reveal that the reaction rate decreases slightly with increase in the
concentration of H+. The plot of k2 versus [H+] is linear (r = 0.989) with a negative slope
(Figure 2), establishing the inhibitory role of H+. The result obtained in the present study can
be rationalized if NBP itself is considered to be the oxidizing species. A similar conclusion
has been arrived at in the oxidation of alkyl phenyl and diphenyl sulphides with NCS24.
104 [H]o, M
Figure 2. Effect of [H+] in the oxidation of PTAA with NBP
The rate of the reaction is not significantly affected by the change in the ionic strength
of the medium (Table 2) brought about by the addition of sodium perchlorate, pointing out
the participation of a neutral species as a reactant in the rate-determining step. The addition
of saccharin has no effect on the rate of oxidation (Table 2), suggesting that the step in
which saccharin is formed as one of the products is not reversible.
Table 2. Influence of ionic strength and phthalimide on reaction rate for the oxidation of
PTAA with NBP at 298 Ka
[I], M
0.216
0.359
0.501
0.609
104kobs, s-1
6.86 0.61
7.46 0.70
8.48 0.68
9.20 0.82
104[phthalimide], M
104kobs, s-1
8.48 0.68
8.24 0.77
8.40 0.74
0
1.0
3.0
aGeneral conditions: [NBP] = 0.0001 M; [PTAA] = 0.002 M; [H+] = 0.00014 M; [I] = 0.501 M
unless otherwise stated; Solvent = 80:20 (v/v) acetonitrile-water

Mechanism of Oxidation of (p-Substituted Phenylthio)acetic Acids
5
The involvement of free-radical intermediates during the reaction can be excluded as
the rate constant is not affected by the addition of acrylonitrile (Table 3). The added KBr has
no effect on the rate of oxidation (Table 3), establishing that the course of the oxidation does
not involve Br+ ion or Br2 as active species. An increase in the water content of acetonitrile-
water solvent system causes an increase in the rate of oxidation (Table 3). A plot of log kobs
versus 1/ε is linear (Figure 3; r = 0.996) with a negative slope indicating that the transition
state is more polarized than the two reactants together in the initial state.
Table 3. Influence of added acrylonitrile (AN), KBr and solvent composition on reaction
rate for the oxidation of PTAA with NCSA at 298 Ka
[AN], M
0
0.003
0.006
104kobs, s-1
8.48 0.68
8.48 0.80
8.56 0.78
[KBr], M
0
0.001
0.002
0.004
104kobs,s-1
% Water (v/v)b
104kobs, s-1
8.48 0.68
21.2 1.6
44.5 3.5
60.6 5.6
8.48 0.68
8.44 0.75
8.49 0.78
8.53 0.78
20
30
40
50
aGeneral conditions: [NCSA] = 0.0001 M; [PTAA] = 0.002 M; [H+] = 0.00014 M; [I] = 0.501 M;
Solvent = 80:20 (v/v) acetonitrile-water unless otherwise stated; bRest was acetonitrile
1/ε
Figure 3. Plot of log kobs versus 1/ε for the oxidation of PTAA with NBP
The effect of substituents at the 4-position of the phenyl ring of PTAA was also studied.
The pseudo-first-order and second-order rate constants for the oxidation of these (p-substituted
phenylthio)acetic acids with NBP at 298 K are collected Table 4. Electron-releasing
substituents in the phenyl ring accelerate the rate, while electron-donating substituents produce
the opposite effect. The log k2 values show excellent correlation with σp values (Figure 4; slope
= -3.22 0.05, r = 0.998). The negative value of ρ indicates an accumulation of positive charge
at the reaction sulphur centre, while the magnitude of ρ value indicates the extent of charge
development on the sulphur atom in the transition state of rate-determining step.
Table 4. Pseudo first-order and second-order rate constants for the oxidation of thioacids,
X-C6H5SCH2COOH by NBP at 298 Ka
X
OMe
Me
H
F
Cl
104kobs, s-1
78.0 6.9
33.9 3.0
8.48 0.68
5.65 0.43
1.73 0.14
0.03 0.00
102k2, M-1s-1
390 35
170 15
42.3 3.5
28.3 2.2
8.65 0.70
0.15 0.00
NO2
bGeneral conditions: [NBP]o = 0.0001 M; [Thioacid]o = 0.002 M; [H+]o = 0.00014 M;
Ionic strength = 0.501 M; Solvent = 80:20 (v/v) acetonitrile-water mixture

6
N.M.I. ALHAJI et al.
σp
Figure 4. Hammett plot for the oxidation of (p-substituted phenylthio)acetic acids by NBP at 298 K
Mechanism
In earlier studies with N-halo compounds in aqueous acid medium, X+, X2, HOX, H2O+X
and >NXH+ are discussed25 to be the probable reactive species. The observation that the
reaction rate is not affected by added phthalimide excludes the possibility of HOBr or
H2O+Br being the reactive species26. The reaction rate is independent of the added KBr
concentration, which indicates that neither bromonium ion nor molecular bromine is
involved in the rate-determining step of the reaction27. Also, the previous studies illustrate
that a first-order dependence of rate of oxidation on [H+] is attributed to the involvement of
H2O+X active species26a, a zero-order dependence to the involvement of the HOX active
species28 and a fractional-order dependence to the involvement of the >NXH+ active
species24,29. In the present investigation, therefore, the negative fractional-order dependence
on [H+] establishes the involvement of NBP itself as reactive species. Based on these kinetic
observations, the following mechanism (Scheme 2) has been proposed.
O
O
H
K
1
(1)
(1)
+
N
Br
N
+
H
Br
O
O
O
O
Ar
HOOCH
k
2
Ar
δ−
N
δ+
S
S
Br
N
+
Br
slow
C
HOOCH
C
2
2
O
O
C
1
(2)
(2)
fast
O
Ar
+
−
S
Br
+
N
HOOCH
C
2
O
Ar
Ar
+
S
fast
+
+
(3)
(4)
+
HBr
Br
+
S
O
H
H O
2
(3)
(4)
HOOCH
C
HOOCH
C
C
2
HOOCH2C
HOOCH2
2
O
O
−
fast
+
N
+
H
NH
O
O
Scheme 2

Mechanism of Oxidation of (p-Substituted Phenylthio)acetic Acids
7
The mechanism in Scheme 2 accounts for the decrease in rate of oxidation with
increasing [H+]. When the concentration of H+ in the reaction solution is increased, more and
more NBP becomes inactive in the form of NBPH+ species (eq. 1), thereby causing a
decrease in the rate of reaction. Similar conclusion has been arrived at in the studies of
oxidation of acetophenone30, aspirin18 and
α
-hydroxy acids31 by NBP, amino acids by
NBS32, secondary amines by CAT32 and L-tyrosine by BAB33, where the N-halo reagent
itself has been proposed as reactive oxidizing species.
The rate law can be expressed as
Rate = k2[NBP][PTAA]
(5)
The high ρ value (-3.22) obtained in the present study provides support for the
chlorosulphonium ion intermediate, (CH2COOH)PhS+Br in the reaction. This conclusion is
further supported by the fact that the present ρ value is analogous to those reported for the
oxidations of organic sulphides with NCS24 (-3.33), NBA34 (-2.37), NBB13 (-3.18), CAT35
36
(-4.25) and Br2 (-3.2), where the intermediacy of such halosulphonium ions has been
proposed.
Conclusion
The NBP oxidation of (p-substituted phenylthio)acetic acids follows a SN2 type mechanism,
in which NBP itself is the oxidizing species. The proposed mechanism has been well
substantiated by substituent effect studies.
Acknowledgement
NMIA thanks UGC, Hyderabad for financial assistance in the form of Minor Research
Project. The authors thank the College Management for providing the necessary facilities.
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